Amprenavir



Better Known as: Agenerase

 * Marketed By: GlaxoSmithKline


 * Major Indication: Human Immunodeficiency Virus Infection


 * Drug Class: HIV Protease Inhibitor
 * Date of FDA Approval (Discontinued): 1999 (2004)


 * 2004 Sales: ~$50 Million
 * Importance: It was the first HIV Protease inhibitor which required only twice-a-day dosing as opposed to every 8 hours. It was replaced by a longer acting prodrug version called Fosamprenavir.
 * See Pharmaceutical Drugs for more information about other drugs and diseases.

Mechanism of Action
When HIV first infects someone, it directs the synthesis of several polyproteins. The maturation of the virus to its infectious form requires that these polyproteins be cleaved to their component proteins by HIV Protease. The subunits of HIV Protease come together to form a catalytic tunnel capable of tightly binding the nascent peptides and cleaving them into their mature, infectious form. Within this tunnel lies two Asp-Thr-Gly conserved sequences, which contain the catalytic Asp residues. These catalytic Asp residues carry out the hydrolytic cleavage of the polyprotein. Amprenavir binds specifically to these conserved sequences within the HIV Protease tunnel, preventing the nascent polyproteins from entering. Unable to actively cleave the nascent proteins into their infectious form, HIV is unable to mature and proliferate, allowing the patients immune system to fight off the infection more easily.

Drug Resistance
The biggest difficulty with treating HIV is the rapidity at which it mutates and becomes resistant to treatments. To view a comprehensive and interactive analysis of the mutations which confer drug resistance to HIV Protease, See: HIV Protease Inhibitor Resistance Profile